Zhang Xiang Yang, Tan Yun-Long, Chen Da-Chun, Tan Shu-Ping, Malouta Michelle Z, Bernard Jared D, Combs Jessica L, Bhatti Sarai, Davis Michael C, Kosten Thomas R, Soares Jair C
Beijing HuiLongGuan Hospital, Peking University, Beijing, China; Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Beijing HuiLongGuan Hospital, Peking University, Beijing, China.
Psychoneuroendocrinology. 2016 Jun;68:140-7. doi: 10.1016/j.psyneuen.2016.03.002. Epub 2016 Mar 5.
Literature suggests that alterations in the inflammatory and immune systems are involved in the pathogenesis of schizophrenia. Specifically, patients diagnosed with schizophrenia exhibit increased IL-18, a pleiotropic proinflammatory cytokine in type 1 T-helper (Th1) responses. The functional 607A/C promoter polymorphism of the IL-18 gene is also associated with the psychopathology of this disorder. However, no current study has explored its role in the clinical symptoms of schizophrenia as mediated through IL-18 levels. We recruited 772 inpatients with schizophrenia and 775 healthy controls in a Han Chinese population and genotyped the IL-18-607A/C polymorphism. Patient psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). Serum IL-18 levels were measured in 80 patients and 93 healthy controls. Our results showed that there were no significant differences in the distribution of the allele and genotype frequencies between the patients and controls. Both increased IL-18 serum level and the IL-18-607A/C polymorphism were positively associated with the PANSS general psychopathology subscore and the PANSS total score. Moreover, interaction of increased IL-18 serum level and the IL-18-607A/C polymorphism influenced the clinical psychopathological symptoms, indicating that association of IL-18 level with the PANSS general psychopathology subscale or the total scores was present only among patients carrying the C allele. We demonstrate an association between the IL-18-607A/C variant and clinical psychopathological symptoms in schizophrenia. Findings suggest that the association between higher IL-18 levels and clinical symptoms in schizophrenia is dependent on the IL-18-607A/C polymorphism.
文献表明,炎症和免疫系统的改变与精神分裂症的发病机制有关。具体而言,被诊断为精神分裂症的患者表现出白细胞介素-18(IL-18)升高,IL-18是1型辅助性T细胞(Th1)反应中的一种多效促炎细胞因子。IL-18基因的功能性607A/C启动子多态性也与该疾病的精神病理学相关。然而,目前尚无研究探讨其通过IL-18水平介导在精神分裂症临床症状中的作用。我们在汉族人群中招募了772例精神分裂症住院患者和775名健康对照,对IL-18 - 607A/C多态性进行基因分型。使用阳性和阴性症状量表(PANSS)评估患者的精神病理学。在80例患者和93名健康对照中测量血清IL-18水平。我们的结果表明,患者和对照之间的等位基因和基因型频率分布没有显著差异。IL-18血清水平升高和IL-18 - 607A/C多态性均与PANSS一般精神病理学亚评分和PANSS总分呈正相关。此外,IL-18血清水平升高与IL-18 - 607A/C多态性的相互作用影响临床精神病理症状,表明IL-18水平与PANSS一般精神病理学亚量表或总分之间的关联仅存在于携带C等位基因的患者中。我们证明了IL-18 - 607A/C变异与精神分裂症临床精神病理症状之间的关联。研究结果表明,精神分裂症中较高的IL-18水平与临床症状之间的关联取决于IL-18 - 607A/C多态性。